title: Effect of the histone deacetylase inhibitors on behavioural sensitization to a single morphine exposure in mice.
abstract: Behavioural sensitization to a single morphine exposure has been considered to be a long-term form of behavioural plasticity associated with opioid addiction. Accumulated evidence has shown that histone modification plays a key role in behavioural plasticity. Therefore, this study was designed to investigate whether the histone deacetylase inhibitors sodium butyrate (SB) and valproic acid (VPA) could disrupt behavioural sensitization to a single morphine exposure. Mice were pretreated with a single injection of morphine and elicited subsequent behavioural sensitization by a challenge-dosage of morphine after a 7-day drug-free period. At doses that did not affect the locomotor activity, both SB and VPA inhibited the acute morphine induced hyperactivity and significantly attenuated the development of behavioural sensitization to a single morphine exposure. Furthermore, the combination of SB and VPA at the sub-effective doses could additionally reduce the development of morphine sensitization. Western blot analysis revealed that multiple administration with the effective dose of SB (160 mg/kg, i.p.) or VPA (150 mg/kg, i.p.) in the behavioural experiments induced hyperacetylation of histone H3 in the NAc of mice. Taken together, these findings suggest that histone acetylation may be involved in morphine sensitization.
authors.affiliation: Department of Physiology, Tianjin Medical University, Tianjin 30070, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Wang-Jun
authors.initials: WJ
authors.lastname: Qin
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Yan-Ting
authors.initials: YT
authors.lastname: Wang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
mesh_terms: D000107:Acetylation; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D014635:Valproic Acid; D009020:Morphine